The general aim of this project is to obtain an understanding of the multiple factors possibly related, either singly or in combination, to the pathogenesis of neurological diseases. Focus is currently placed on multiple sclerosis (MS). Particular attention is being given to genetic and immunological factors. Studies of genetic influence include examination of genes encoding for HLA molecules and the antigen receptor on T cells (T-cell receptor). These studies are performed in patients with sporadic disease, members of families with multiple effected members, and identical or nonidentical twins either concordant or discordant for MS. Parallel studies are being conducted in diseases which have a clinical presentation similar to MS. In order to contribute to the interpretation of findings in MS, tropical spastic paraparesis (TSP) related to infection with HTLV-I is being evaluated with regard to both clinical and neuroimaging characteristics. Other diseases affecting cerebral white matter such as Sjogren's disease and familial leukodystrophy are being examined by neuroimaging techniques. The double-blind portion of a phase III multicenter trial of cyclosporine A in the treatment of MS has been completed. Studies of patients in the open label phase focus on the relationship between cyclosporine treatment and nephrotoxicity.